摘要:

SummaryInterferon‐gamma (IFN‐γ) production by peripheral blood mononuclear leucocytes (MNL) is reduced in atopic dermatitis (AD) patients. This may be related to abnormalities in second messenger systems, and increased prostaglandin E2(PGE2) release from monocytes. We compared the effects of manipulating the second messenger activity using the phosphodiesterase (PDE) inhibitor Ro 20‐1724, dibutyryl cyclic adenosine monophosphate (cAMP), and cyclooxygenase inhibition of PGE2, on IFN‐γ production by cultured MNL from AD patients (n=9) and normal controls (n=10).Ficoll‐Hypaque‐separated MNL were cultured for 48 h with OKT3 stimulation, and cAMP, Ro 20‐1724, or indomethacin. Supernatants were analysed for IFN‐γ by ELISA. Basal IFN‐γ was lower in AD patients, and the increase in IFN‐γ production with OKT3 was 6.5‐fold greater in control subjects than patients with AD. Culture with indomethacin significantly enhanced OKT3‐stimulated IFN‐γ production in both groups, whereas OKT3‐stimulated IFN‐γ production was abolished with dibutyryl cAMP. IFN‐γ production was significantly lower with Ro 20‐1742 in AD than in normal controls.We have shown reduced IFN‐γ release from unstimulated and stimulated MNL in AD patients compared with normal controls. The addition of indomethacin increased IFN‐γ production in both groups, although the increase was less in AD patients, suggesting an intrinsic cellular defect. IFN‐γ release from AD MNL was more sensitive to the inhibitory effects of PDE, and this may be due to increased PDE activity,

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb02484.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb15387.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryIt has previously been shown that circulating Sézary cells respondin vitroto superantigenic staphylococcal exotoxins in a manner that is restricted by their Vß usage. This study was conducted to examine whether cutaneous colonization withStaphylococcus aureusinfluences the activity of the skin lesions of Sézary syndrome, and whetherS. aureusisolated from patients with Sézary syndrome stimulates circulating Sézary cellsin vitro. Two patients with Sézary syndrome, whose skin was colonized withS. aureus, were treated with antibacterial agents, and the relation between the severity of the skin disease and the degree ofS. aureuscolonization was assessed. In addition, the patients' peripheral blood mononuclear cells were cultured in the presence of mitomycin C‐treatedS. aureusor superantigenic staphylococcal toxins. The antibacterial treatment improved the skin disease, and eliminatedS. aureusin both patients. In one patient, 98% of the peripheral blood mononuclear cells bore Vα2Vß17 of the T‐cell receptor, indicative of the presence of an extremely high percentage of circulating Sézary cells. The peripheral blood lymphocytes from this patient responded wellin vitroto superantigenic staphylococcal enterotoxin (SE), but not to SEA or toxic shock syndrome toxin‐1, or to mitomycin‐treatedS. aureusisolated from the same patient. Cutaneous colonization byS. aureusinfluences the disease activity of CTCL, possibly by activation of Sézary cells by bacterial superanti

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb02485.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb15388.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryIn the present study, we investigated the expression of the tumour suppressor protein p53 in 1 primary and 43 metastatic malignant melanomas by immunohistochernistry, and correlated the findings with clinicopathological parameters such as histological melanoma subtype, thickness of primary melanomas (Breslow thickness) and patient outcome.In primary melanomas, the polyclonal anti‐p5 3 antibody CM‐1 detected immunoreactivity in 70% of the lesions, predominantly in the cytoplasm. Signals were observed in this cellular compartment in 57% of the melanomas, whereas in 32% nuclear p53 over‐expression was detected. Immunohis‐tochemistry, using the monoclonal antibody DO‐1, revealed lower staining frequencies. However, both antibodies showed congruent results in approximately 80% of the cases. Overall, immuno‐reactivity was observed in 73% of superficial spreading melanomas, but only in 52% of lentigo maligna melanomas. This difference (P<0.001) was mainly due to a lower frequency of cytoplasmic immunoreactivity (P<0.002). There was no difference with respect to cytoplasmic and nuclear immunoreactivity between thin (<1 mm thickness) and thicker primary melanomas. Staining frequencies detected in metastatic lesions seemed to be lower than in primary tumours. In 103 primary melanomas, follow‐up data for at least 5 years were available. In 71% (54 of 76) of the primary melanomas which did not recur, and in 78% (21 of 27) of tumours with subsequent metastases, p53 over‐expression was detected by CM‐1. However, this difference was not statistically significant.The results of the present study indicate that immunoreactivity to anti‐p53 antibodies is a common observation in malignant melanomas, with staining signals predominantly found in the cytoplasm of cells. The observation of similar staining frequencies in thin, thick and metastatic lesions indicates that p53 over‐expression is an early event in the pathogenesis of malignant melanoma. However, the immunohistochemical detection of p53 in primary melanomas is not

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb02487.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb15389.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summaryp53 is an oncosuppressor gene located on chromosome 17p. Point mutations of the p53 gene are seen frequently in human malignancies, and are closely associated with malignant transformation under in vitro conditions. Mutated p53 protein shows a slow cell turnover rate, and accumulates in cells at the nuclear and/or cytoplasmic level. As a result, mutated p53 protein can be detected more readily by immunohistology than the wild‐type protein. In this study, we used a monoclonal anti‐p53 antibody (clone D07) to examine the expression of p53 protein in 25 cutaneous T‐cell lymphomas (CTCL) of low‐ and high‐grade malignancy, i.e. mycosis fungoides (n = 6), Sézary's syndrome (n = 2), and large cell lymphomas of pleomorphic (n = 14) or anaplastic (n= 3) subtype. The results showed that easily detectable p53 protein was present in many of the neoplastic cells in half of the high‐grade lymphomas. In contrast, in the low‐grade lymphomas no, or only very few, p53‐positive neoplastic cells could be detected. These findings suggest that molecular and/or genetic alterations of p53 may be implicated in the pathogenesis of high‐grade CTCL, but are unlikely to be of critical importance

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb02488.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryPlasma levels of 8‐methoxypsoralen (8‐MOP) were determined by high‐pressure liquid chromato‐graphy in 19 patients with psoriasis who were receiving bath‐PUVA treatment, at different time points after the psoralen bath. The levels of 8‐MOP varied between<5 ng/ml (lower limit of detection) and 34 ng/ml, and we found a relationship between the plasma psoralen levels and the severity of

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb02489.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryMK‐886, a leukotriene biosynthesis inhibitor, which prevents the translocation and activation of 5‐lipoxygenase. has been proposed as an effective drug for the treatment of inflammatory disorders, including psoriasis. In the present study, we investigated the effects of MK‐886 on calmodulin as a potential target protein of anti‐inflammatory drug activity, and on the proliferation of cultured human keratinocytes, a calmodulin‐dependent cellular response with indicative value for antipsor‐iatic drug activity. Despite potent calmodulin‐antagonistic activity in vitro, MK‐886 failed to block cell proliferation in a human keratinocyte line, whereas trifluoperazine, a well characterized calmodulin antagonist with similar effects on calmodulin activity in ourin vitroassays, inhibited cell proliferation in a dose‐dependent manner. Further investigations on the mechanism of action revealed that, in contrast with trifluoperazine, calmodulin antagonism by MK‐886in vitrois likely to be mediated at the level of the allosteric calmodulin‐recognition site of phosphodiesterase, rather than by binding to calmodulin itself. Therefore, our data do not conflict with the proposed role of calmodulin in the regulation of cell proliferation, but demonstrate that drug‐induced antagonism of calmodulin, detected by inhibition of calmodulin‐dependent enzymesin vitro, is not necessarily linked to antiproliferative activi

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb02490.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0007-0963    

DOI:10.1111/j.1365-2133.1995.tb15390.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY